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Objective: This study investigated prescribing patterns of two cohorts of patients treated with selective serotonin reuptake inhibitors (SSRI) in primary care in Wales (UK), to better understand drivers for increased usage. Methods: This e‐cohort study included patients receiving a first READ‐coded SSRI prescription in SAIL in either 2005 or 2015. Patients were followed up for 3 years from date of SSRI prescription. Influence of age and other demographic data on prescribing patterns, and details of mental health or medication reviews that took place were identified. Results: In total 67,006 patients were included across the two cohorts; 29,534 in 2005, and 37,472 in 2015. Citalopram was the most commonly prescribed SSRI in both cohorts. A READ‐coded diagnosis relating to SSRI treatment could not be identified in 24,797 patients. The percentage of patients continuing treatment for 3 years was 6.9% and 11.3% in 2005 and 2015, respectively. In total, 21,150 (72%) patients in the 2005 cohort and 23,947 (64%) in the 2015 cohort received at least one medication review during follow‐up. Conclusions: The proportion of patients continuing longer term treatment was small, whilst the number of recorded mental health and medication reviews offers some reassurance that prescribing remained appropriate. [ABSTRACT FROM AUTHOR]

Background: In placebo‐controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure. In this study, we investigated the effect of reboxetine and citalopram on anal opening pressure in healthy female volunteers. Methods: In a double‐blind, three‐way crossover trial, 24 female participants received single doses of 40 mg citalopram, 8 mg reboxetine, and matching placebos, with a minimum of 8‐day washout between sessions. Using anal acoustic reflectometry, we measured anal opening pressure during both resting and squeezing conditions at the estimated time of peak plasma concentration for both study drugs. Key Results: Compared with placebo, reboxetine increased anal opening pressure with 23.4 cmH2O (95% confidence interval [CI] 16.5–30.2, p < 0.001) during rest and with 22.5 cmH2O (95% CI 15.2–29.8, p < 0.001) during squeeze. Citalopram did not change anal opening pressure statistically significantly compared to placebo. Conclusions & Inferences: An 8‐mg dose of reboxetine increased anal opening pressure substantially in healthy women, suggesting potential benefits for fecal incontinence symptoms. In contrast, a 40‐mg dose of citalopram showed a marginal and statistically insignificant effect on anal opening pressure, indicating that selective serotonin reuptake inhibitors do not contribute to fecal incontinence by reducing anal sphincter tone. [ABSTRACT FROM AUTHOR]

Pharmaceuticals have been classified as an environmental concern due to their increasing consumption globally and potential environmental impact. We examined the toxicity of sediment‐associated diclofenac and citalopram administered as both single compounds and in a mixture to the sediment‐living amphipod Corophium volutator. This laboratory‐based study addressed the following research questions: (1) What is the toxicity of sediment‐associated diclofenac and citalopram to C. volutator? (2) Can the mixture effect be described with either of the two mixture models: concentration addition (CA) or independent action (IA)? (3) What is the importance of the choice of (i) exposure measure (start concentration, time‐weighted average [TWA], full exposure profile) and (ii) effect model (concentration–response vs. the toxicokinetic–toxicodynamic model general unified threshold model for survival in its reduced form [GUTS‐RED]) for the derived effect concentration values? Diclofenac was more toxic than citalopram to C. volutator as a single compound (10‐day exposure). Diclofenac exposure to C. volutator provided median lethal concentrations (LC50s) within the same range (11 µg g−1 dry wt sediment) using concentration–response based on TWA and both GUTS‐RED models. However, concentration–response based on measured start concentrations provided an approximately 90% higher LC50 (21.6 ± 2.0 µg g−1 dry wt sediment). For citalopram, concentration–response parameters were similar regardless of model or concentration used (LC50 85–97 µg g−1 dry wt sediment), however, GUTS‐RED with the assumption of individual tolerance resulted in a lower LC50 (64.9 [55.3–74.8] µg g−1 dry wt sediment). The mixture of diclofenac and citalopram followed the CA quite closely, whereas the result was synergistic when using the IA prediction. In summary, concentration–response based on TWA and GUTS‐RED provided similar and reasonably good fits compared to the data set. The implications are that GUTS‐RED will provide a more flexible model, which, in principle, can extend beyond the experimental period and make predictions based on variable exposure profiles (toxicity at different time frames and at different variable exposure scenarios) compared to concentration–response, which provides contaminant toxicity at one point in time. Environ Toxicol Chem 2024;43:1767–1777. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. [ABSTRACT FROM AUTHOR]

A cohort study examining treatment outcomes for older adults in Denmark has found substantial variation in results from commonly used antidepressants. Most of the individual antidepressants were associated with a higher risk of treatment discontinuation and adverse events compared with sertraline, the antidepressant that is recommended as first‐line treatment in Danish clinical guidelines. Study results were published online Oct. 18, 2023, in the American Journal of Psychiatry. [ABSTRACT FROM AUTHOR]

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)‐evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C‐administrated groups. Furthermore, vitamin C administration markedly alleviated CTL‐induced nitro‐oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL‐positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL‐induced testicular damage via mitigating nitro‐oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug‐associated reproductive toxicity and male sub/infertility. [ABSTRACT FROM AUTHOR]

Authors of a study of maintenance treatment with an adjunctive antidepressant in patients with bipolar I disorder and remitted depression concluded that 52 weeks of treatment did not result in significant improvement in time to occurrence of any mood episode compared with an 8‐week regimen. However, the study did suggest more favorable results for the longer‐term treatment in preventing relapse to depression. Study results were published Aug. 3, 2023, in the New England Journal of Medicine. [ABSTRACT FROM AUTHOR]

Citalopram (generic) — Celexa (brand) [ABSTRACT FROM AUTHOR]

Recent research has revealed various lethal and sublethal effects of the selective serotonin reuptake inhibitor citalopram hydrobromide on the harpacticoid copepod Nitocra spinipes. In the present study, an individual‐based model (IBM) grounded in the dynamic energy budget (DEB) theory was developed to extrapolate said effects to the population level. Using a generic DEB‐IBM as a template, the model was designed to be as simple as possible, keeping model components that are outside the scope of the core DEB theory to a minimum. To test the model, a 56‐day population experiment was performed at 0, 100, and 1000 μg citalopram hydrobromide L−1. In the experiment, the populations quickly reached a plateau in the control and at 100 μg L−1, which was correctly reproduced by the model and could be explained by food limitations hindering further population growth. At 1000 μg L−1, a clear mismatch occurred: Whereas in the experiment the population size increased beyond the supposed (food competition–induced) capacity, the model predicted a suppression of the population size. It is assumed that the IBM still misses important components addressing population density–regulating processes. Particularly crowding effects may have played an important role in the population experiment and should be further investigated to improve the model. Overall, the current DEB IBM for N. spinipes should be seen as a promising starting point for bioenergetics‐based copepod population modeling, which—with further improvements—may become a valuable individual‐to‐population extrapolation tool in the future. Environ Toxicol Chem 2023;42:1094–1108. © 2023 SETAC [ABSTRACT FROM AUTHOR]

Many drugs are associated with QT prolongation and certain patient factors can increase this effect, leading to a significant risk of arrhythmias. This article describes the drug and patient factors that can lead to QT prolongation and discusses how the risks can be reduced. [ABSTRACT FROM AUTHOR]

Sexual disinhibition in dementia is a distressing and embarrassing behaviour. Currently, there are no guideline‐directed management aims to address this behaviour in patients with dementia. This case report highlights a combined non‐pharmacological and pharmacological approach for managing dementia in a patient who showed marked sexual disinhibition. [ABSTRACT FROM AUTHOR]

The selective serotonin reuptake inhibitors (SSRIs) citalopram and escitalopram are associated with QT prolongation, which increases the risk of serious arrhythmia. Consequently, regulatory agencies issued safety warnings in 2011. This study aimed to investigate the risk of serious arrhythmia following initiation of citalopram or escitalopram compared to other SSRIs and the risk in the periods before and after the warnings were issued. We conducted a series of nationwide cohort studies emulating a target trial using Danish healthcare register data from January 1, 2002, to December 31, 2016. We included patients (aged ≥65 years) who filled an SSRI prescription with a 1‐year washout period before the index date. The outcome was an event of serious arrhythmia. Individuals were followed for a maximum of 6 months using an intention‐to‐treat approach. Log‐binomial regression analyses were performed, estimating risk ratios (RRs) and 95% confidence intervals (CIs) adjusting for age and sex, comorbidities, and comedications with propensity scores. Dose–response effects were not investigated because dosage instructions were not available. We included 167,366 (146,014 individuals), 40,113 (37,069 individuals), and 50,281 (44,754 individuals) person‐trials of citalopram, escitalopram, and other SSRIs, respectively. In total, there were 228 events of serious arrhythmia. No difference in risk was observed in the entire study period for either citalopram (0.87 [0.62–1.22]) or escitalopram (0.85 [0.53–1.40]). We identified lower point estimates after the safety warning, RR 0.54 (95% CI 0.31–0.93) for citalopram and 0.58 (0.20–1.63) for escitalopram. Initiation of citalopram and escitalopram was not associated with an increased risk of serious arrhythmia. However, lower point estimates were observed after the safety warning. [ABSTRACT FROM AUTHOR]

Aims: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. Methods: We conducted a randomized, double‐blind, placebo‐ and active‐controlled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placeboreboxetine), 8 mg reboxetine (and placebocitalopram), or two placebos. Study drugs were administered at a 1‐h interval due to a difference in estimated time to peak plasma concentration (tmax). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated tmax for both study drugs (one timepoint). Results: Compared to placebo, citalopram increased OUP by 6.6 cmH20 (95% confidence interval [CI] 0.04–13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH20 (95% CI: 1.3–12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH20 in resting condition compared to placebo (95% CI: 23.5–36.5, p < 0.001), and 27.0 cmH20 (95% CI: 21.2–32.8, p < 0.001) in squeezing condition. Conclusion: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI. [ABSTRACT FROM AUTHOR]

Drug‐induced QT prolongation, primarily antiarrhythmic drugs, is a common cause of torsade de pointes (TdP). Although there have been previous reports of drug‐induced TdP in patients, it has not been well documented when caused by citalopram during the pacemaker battery‐depletion phase. To improve delirium recognition, we report a case of citalopram‐induced TdP during the pacemaker battery‐depletion phase. An 84‐year‐old Chinese female was brought to the hospital presenting recurrent syncope. She lost consciousness and was admitted after her syncope TdP was documented. Her pacemaker was inspected and found to be operating in an extremely ineffective manner. Although she had prolonged QT interval after the pacemaker was replaced, she did not suffer another syncope attack, and ECG monitoring revealed no cardiac arrhythmia or TdP. During her admission, she was treated with citalopram for depression. Citalopram was discontinued when the QT interval shortened progressively. In this study, we described a case of citalopram‐induced TdP during the depletion phase of a pacemaker battery. This case should serve as a cautionary lesson to clinicians to avoid using citalopram during the pacemaker battery‐depletion phase. [ABSTRACT FROM AUTHOR]

Hardly a week goes by that I don't find myself reading about the "mind‐body connection" in a non‐medical publication. The article is typically focused on some common physical disease (diabetes, arthritis, whatever) that, to the reporter's putative amazement, has just been shown to be affected by psychological or psychiatric factors. If you're a regular reader of the Update, I doubt you'll find such reports surprising. Indeed, when I talk with healthcare providers across specialties, I rarely encounter skepticism about this "connection" — a change, to be clear, from my early days in medicine, when "supratentorial" factors were often noted with borderline derision. [ABSTRACT FROM AUTHOR]

Purpose: Polypharmacy is common in the hemodialysis population and increases the likelihood that patients will be exposed to clinically significant drug–drug interactions. Concurrent use of proton pump inhibitors (PPIs) with citalopram or escitalopram may potentiate the QT‐prolonging effects of these selective serotonin reuptake inhibitors through pharmacodynamic and/or pharmacokinetic interactions. Methods: We conducted a retrospective cohort study using data from the U.S. Renal Data System (2007–2017) and a new‐user design to examine the differential risk of sudden cardiac death (SCD) associated with citalopram/escitalopram initiation vs. sertraline initiation in the presence and absence of PPI use among adults receiving hemodialysis. We studied 72 559 patients:14 983 (21%) citalopram/escitalopram initiators using a PPI; 26 503 (36%) citalopram/escitalopram initiators not using a PPI;10 779 (15%) sertraline initiators using a PPI; and 20 294 (28%) sertraline initiators not using a PPI (referent). The outcome of interest was 1‐year SCD. We used inverse probability of treatment weighted survival models to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Compared with sertraline initiators not using a PPI, citalopram/escitalopram initiators using a PPI had the numerically highest risk of SCD (HR [95% CI] = 1.31 [1.11–1.54]), followed by citalopram/escitalopram initiators not using a PPI (HR [95% CI] = 1.22 [1.06–1.41]). Sertraline initiators using a PPI had a similar risk of SCD compared with those not using a PPI (HR [95% CI] = 1.03 [0.85–1.26]). Conclusions: Existing PPI use may elevate the risk of SCD associated with citalopram or escitalopram initiation among hemodialysis patients. [ABSTRACT FROM AUTHOR]

The 2,3‐dihydrobenzofuran heterocyclic systems are found in various biologically active natural and pharmaceutical products of biological relevance such as Phalarine, Rocaglamide, and Furaquinocin A. The interest in the study of 2,3‐dihydrobenzofurans is constantly increasing because of their numerous biological properties such as anti‐tumor, anti‐cancer, anti‐tubercular, and anti‐malarial activities. Different methods have been established towards the synthesis of 2,3‐dihydrobenzofurans involved via intra‐ and inter‐molecular reactions. Besides, the 1,3‐dihydroisobenzofuran structure has been identified as a fundamental nucleus in many natural products, bioactive compounds, and functional molecules (e. g., Pestacin, Isopestacin, Citalopram, Xylarinol B, Matriisobenzofuran, Thunberginol F7‐O‐β‐D‐glucopyranoside). On the other hand, 1,3‐disubstituted isobenzofurans are powerful structural motifs with a wide range of biological activities, like anti‐inflammatory, anti‐histaminic, and anti‐HIV. In the last few years, a decent number of diligent synthetic approaches have been demonstrated toward synthesizing 1,3‐disubstituted isobenzofurans. This review focuses on the effective synthetic routes developed to construct 2,3‐dihydrobenzofurans and 1,3‐dihydroisobenzofurans and their applications in recent years. [ABSTRACT FROM AUTHOR]

The article reports that lack of engagement in the common therapies for anxiety disorders include reluctance to take medication and restricted access to cognitive-behavioral therapy heightened the importance of identifying more acceptable treatments. Topics include examines with mindfulness-based interventions gaining popularity, and some research suggests that meditation can reduce anxiety as investigators conducted a trial comparing the effectiveness of mindfulness-based stress reduction.

Recent evidence suggests that treatment with antidepressants may promote functional recovery. However, the timeframe in which these pharmacological agents can influence stroke recovery is not well understood. This research investigated whether delayed administration of citalopram, used clinically in the management of post‐stroke depression, could improve long‐term functional recovery following experimental stroke. MacGreen mice carrying an enhanced green fluorescent protein reporter gene in monocyte and macrophage populations were subjected to 45 min occlusion of the middle cerebral artery. Animals were administered citalopram (10 mg/kg/day, n = 20) or saline (n = 20) starting 3 days after stroke for 28 days. Neurological deficits and skilled motor performance in the staircase task were recorded for 9 weeks post stroke. Grey and white matter structural lesions were quantified at Week 9, and enhanced green fluorescent protein immunohistochemistry was used to evaluate the effect of citalopram on inflammation. Twenty‐five animals were included in the final analysis. Citalopram‐treated animals (n = 13) showed a significant increase in impaired forepaw use in the staircase task compared with saline‐treated animals (n = 12) 2, 3 and 7 weeks post stroke but no difference in neurological score at any time point examined. Citalopram treatment was associated with decreased monocyte/macrophage cell density and increased white matter tract integrity within the ipsilateral cortex. In conclusion, delayed administration of citalopram decreased brain inflammation and produced functional gains in our mouse model of stroke. Beneficial effects on skilled motor functions were long‐lasting. [ABSTRACT FROM AUTHOR]

Normal‐phase and reversed‐phase high‐performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)‐enantiomer impurity have been developed on the cellulose‐based Chiralcel OJ‐H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol–water–diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)‐enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL−1, respectively. [ABSTRACT FROM AUTHOR]

Two methods using LC–MS/MS were validated to quantify citalopram (CTP) racemate [(R/S)‐CTP] and the enantiomers (R)‐CTP and (S)‐CTP in human plasma, respectively. Paroxetine hydrochloride was used as the internal standard, and samples were extracted by protein precipitation with acetonitrile. The non‐enantioselective method was conducted using a C18 column, and the mobile phase consisted of water for solvent A and acetonitrile for solvent B, both with 0.1% formic acid. For the chiral method, an analytical column Lux Cellulose‐1 was used. Mobile phase A was composed of water with 0.025% of formic acid and 0.05% of diethylamine, and mobile phase B consisted of acetonitrile:2‐propanol (95:5, v/v). No significant matrix effects were observed at the retention times of analytes and internal standard. The mean recovery was 89%, and the assays were linear in the concentration range of 1–50 and 5–30 ng/mL for the non‐enantioselective and enantioselective methods, respectively. The intra‐ and inter‐day precisions of both methods were less than 12.30%, and the accuracies were less than 12.13%. The validated methods were successfully applied to a pharmacokinetic study in which 20‐mg CTP tablets were administered to healthy volunteers, and their plasma levels were monitored over time in a bioequivalence study. Highlights: Simple and rapid LC–MS/MS method for the quantification of citalopram and its enantiomers in human plasma.Both methods were demonstrated to be selective, reliable, and sensitive.Both methods have sufficient sensitivity to quantify the steady state through concentrations already reported for citalopram and escitalopram.Validated method presented in this study can be suitably applied to pharmacokinetic studies involving citalopram and escitalopram.Bland–Altman analysis suggested that non‐enantioselective and enantioselective methods can be applied in pharmacokinetic studies. [ABSTRACT FROM AUTHOR]

Escitalopram (generic) – Lexapro (brand) [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year-old male with late-onset obsessive–compulsive disorder with memory obsessions. Topics include Obsessive–compulsive disorder (OCD) being a chronic illness characterized by recurrent intrusive thoughts; and names of persons, shops, addresses, or number plates of passing vehicles.

Exposure to stressful life events and individual differences in the personality trait neuroticism are important risk factors that interact to predict major depressive disorder (MDD). Less is known about their effect on treatment response in depression. Here, we examine whether stressful life events experienced prior to and during treatment interact with neuroticism to predict response to 16‐week pharmacotherapy for MDD. Participants included 159 outpatients with MDD who were initially treated with 8 weeks of escitalopram. Those who responded to the initial treatment continued on escitalopram monotherapy, whereas non‐responders received 8 weeks of adjunctive aripiprazole. Personality was assessed using the NEO‐Five Factor Inventory, and stressful life events were assessed using the Life Events and Difficulties Schedule, a rigorous contextual interview that includes independent ratings of threatening life events. High baseline neuroticism was associated with a lower likelihood of response when patients experienced one or more negative life events before treatment. Secondary analyses indicated that this effect was specific to neuroticism, and not better accounted for by its self‐criticism or negative affect facets. Our results suggest that assessing personality and stressful life events at baseline can help clinicians assess which patients will respond to antidepressant therapy and which may need treatment augmentation. [ABSTRACT FROM AUTHOR]

Use of psychotropic medicines such as antipsychotics, antidepressants, and anxiolytics is common in children with autism spectrum disorder (ASD); however, very little is known about medicine use in adults with ASD. This pilot project aimed to describe medicines use in Australian adults with ASD. We conducted a retrospective analysis of mental health care plan records for adults with a confirmed diagnosis of ASD from a single metropolitan psychology practice. One hundred and twenty one of the 168 participants (72%) were taking at least one medicine. Fifty‐nine of the 168 persons whose care plans were reviewed (35%) were taking an antidepressant, the most frequently prescribed psychotropic medicine. Twenty‐three (14%) were prescribed a medicine for airways disease, most commonly salbutamol. Antipsychotics were used by 11% and anxiolytic/hypnotics by 10%. The most commonly used antidepressants were sertraline and escitalopram (21 and 19% of antidepressant users, respectively). The most commonly used antipsychotics were quetiapine and risperidone (32% and 27%, respectively). This pilot project has highlighted that use of psychotropic medicines is common in adults with ASD. [ABSTRACT FROM AUTHOR]

Objectives: Geriatric depression is common and is often associated with coexisting medical illnesses, cognitive dysfunction, or both. Treatment with pharmacotherapy is usually required, and many patients may not respond to initial therapy. Thus, there is a need for adjunctive treatment options. The objective of this systematic review is to assess the efficacy and safety of methylphenidate (MPH) in the treatment of geriatric depression. Methods: PubMed (1946–December 2020) and Embase (1947–December 2020) were queried using the following search terms: geriatrics, aged, geriatric patient, or elderly and depressive disorder, depression, major depression or late‐life depression, and MPH. Studies were included if they were a randomized‐controlled trial or open‐label trial that investigated use of MPH for treatment of depression in adults aged 60 years and older. Results: After screening per the inclusion criteria, five prospective trials were included. All studies found improvement in depressive symptoms with use of MPH or MPH combined with citalopram. Study durations ranged from 8 to 16 weeks and MPH dosing ranged from 5 to 90 mg per day. Conclusions: Based on the reviewed literature, MPH appears to be most effective when combined with citalopram and used short‐term. MPH should be initiated at a low dose and titrated up to 10 or 20 mg per day based on response. Larger, long‐term trials are needed to further define the role of MPH in this population. Key points: Adjunctive treatment for geriatric depression is often requiredMethylphenidate (MPH) has been used for treatment of geriatric depression, but available evidence is limitedMPH appears to be most effective combined with citalopram and used short‐term [ABSTRACT FROM AUTHOR]

The global consumption of human antidepressants has steadily increased over the last years. The most widely prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs), which have been linked to various life‐history effects in nontarget organisms. We investigated the effects of the SSRI citalopram hydrobromide on the life history of the copepod Nitocra spinipes. Slight but significant developmental delay effects were observed at nominal concentrations of 0.1 and 1 µg/L, with stronger effects occurring at measured concentrations of 178 µg/L and above. At 77 µg/L and above, a significant increase in adult body length and offspring production/brood was found, although the time between brood releases remained unaffected. The pre‐adult surviving fraction was significantly reduced (by 44%) at 765 µg/L. For a mechanistic evaluation of these observations, we used a bioenergetics model for N. spinipes based on the dynamic energy budget theory. Toxicokinetic and toxicodynamic submodels were used to dynamically simulate the chemical uptake and elimination, as well as dose–response relationships for hypothetical physiological modes of action and survival over time. Although none of the commonly invoked physiological modes of action, acting on assimilation, maintenance, growth, or offspring production, could explain the observed combination of effects, a newly proposed physiological mode of action acting on the process of maturation delivered correct predictions in terms of each effect's direction. The model fits could be further improved by allowing for a gentler concentration–effect slope and by adding an auxiliary physiological mode of action acting on the reproduction efficiency. The quantitative explanations provided in the present study offer a starting point for exploratory simulation studies investigating the effects of SSRIs at higher ecological levels. Environ Toxicol Chem 2021;40:1928–1939. © 2021 SETAC [ABSTRACT FROM AUTHOR]

Objectives: This randomized open‐label trial compared the efficacy and tolerability of vortioxetine (15 mg/daily) with different antidepressants in the treatment of patients with burning mouth syndrome (BMS). Methods: One and hundred fifty BMS patients were randomized into five groups and treated with either vortioxetine, paroxetine (20 mg/daily), sertraline (50 mg/daily), escitalopram (10 mg/daily) or duloxetine (60 mg/daily). The Visual Analogue Scale (VAS), Total Pain Rating Index (T‐PRI), Hamilton Rating Scales for Depression (HAM‐D) and Anxiety (HAM‐A), and Clinical Global Impression Improvement (CGI‐I) and Efficacy scales (CGI‐E) were performed at baseline and after 2, 4, 6, and 12 months of treatment. Any adverse events (AEs) were tabulated for each group. Descriptive statistics, including the Kruskal–Wallis non‐parametric test and the Friedman non‐parametric test for median comparisons between different times, were used. Results: All the antidepressants (AD) were associated with a significant decrease in the VAS, T‐PRI, HAM‐A, HAM‐D, CGI‐I, and CGI‐E scores in the long‐term (p <.001). However, the response rate of the vortioxetine group showed a significant reduction after six months. The medians, after 6 months, were as follows: VAS 0.0; T‐PRI 2.0; HAM‐A 7.0; HAM‐D 7.0; CGI‐I 1.0; and CGI‐E 1.0 with a lower incidence of AEs (p <.019). Conclusion: Vortioxetine was efficacious with a shorter latency of action and fewer AEs compared with other ADs. [ABSTRACT FROM AUTHOR]

Objective: Since several recent meta‐analyses report a dose‐response relationship for the antidepressant effect of the selective serotonin reuptake inhibitors (SSRIs), we investigated how these drugs are dosed in clinical practice. Methods: Through linkage of nation‐ or region‐wide registers, we describe SSRI doses in 50,365 individuals residing in Region Västra Götaland, Sweden, with an incident diagnosis of depression and initiating SSRI treatment between 2007 and 2016. The primary question was to elucidate to what extent these individuals had been prescribed a daily dose that according to recent meta‐analyses is required to elicit the maximum antidepressant effect, that is >20 mg citalopram, >10 mg escitalopram, >10 mg fluoxetine, >10 mg paroxetine or >50 mg sertraline. Results: In all, 21,049 (54%) out of 38,868 individuals <65 years of age, and 9,131 (79%) out of 11,497 individuals ≥65 years of age, never received an SSRI dose reported to exert maximum antidepressant effect. These prescribing practices were seen for citalopram, escitalopram and sertraline, but not for fluoxetine and paroxetine, and were frequent in both primary and secondary/tertiary care. Suggesting that doses here defined as maximum efficacy doses, when prescribed, are usually not intolerable, between 59% and 68% of individuals <65 years of age received such a dose also for the subsequent prescription, that is as frequently as in those prescribed a sub‐maximum efficacy dose (52–69%). Conclusion: Most patients being prescribed an SSRI to treat their depression never receive the dose that according to recent meta‐analyses is most likely to effectively combat their condition. The lack of consensus regarding effective dosing of SSRIs may have contributed to this state of affairs. [ABSTRACT FROM AUTHOR]

Patients receiving citalopram as adjunctive treatment for bipolar depression experienced no significant improvement relative to placebo in a clinical trial that measured both acute and maintenance treatment response. This was the first study to evaluate the efficacy of a serotonin reuptake inhibitor (SRI) for the maintenance treatment of bipolar depression. Results were published online Jan. 12 in the Journal of Clinical Psychiatry. [ABSTRACT FROM AUTHOR]

The article presents the discussion on Selective serotonin reuptake inhibitors (SSRIs) considering the primary treatment option for patients with panic disorder. Topics include comparing the effectiveness of SSRIs and other medications in the treatment of panic disorder with or without agoraphobia; and comparing drug interventions and reporting on the outcomes of remission, dropout, anxiety symptoms, depressive symptoms, quality of life.

Background: Esophageal hypersensitivity is considered an important pathophysiological mechanism in refractory gastroesophageal reflux disease (GERD) patients. Serotonin (5‐HT) plays an important role in the regulation of GI (gastrointestinal) secretion, motility and sensitivity. Previous studies found that altered 5‐HT availability has no clear effects on esophageal/GI sensations. Our aim was therefore to investigate the role of 5‐HT in esophageal sensitivity in healthy volunteers (HV). Methods: Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 3 different placebo‐controlled studies. In the first study, the effect of citalopram (40 mg; 5‐HT reuptake inhibitor; intravenous) was investigated (n = 14). In the second study, the effect of buspirone (20 mg; 5HT1A agonist; oral) was investigated (n = 10). In the third study, acute tryptophan depletion (ATD) was used to decrease 5‐HT levels to investigate the effect of reduced 5‐HT availability on esophageal sensitivity (n = 15). Key Results: No difference was observed in esophageal sensitivity after the administration of citalopram or buspirone (all p > 0.06). In contrast, pain perception threshold to chemical stimulation was increased after ATD (p = 0.017, Cohen's d+ = 0.67). No effect was found on the first perception or pain tolerance threshold. ATD had no influence on esophageal sensitivity to thermal, mechanical, and electrical stimulation compared with placebo. Conclusions and Inferences: ATD, which induces 5‐HT depletion, significantly decreased pain perception threshold during chemical stimulation, without affecting sensitivity to mechanical, thermal, or electrical stimulation. These findings confirm the involvement of 5‐HT in the control of esophageal acid sensitivity, but identifying the receptors involved requires more ligands and studies. [ABSTRACT FROM AUTHOR]

Escitalopram reduces anxiety symptoms in adolescents, but pharmacogenetics variables influence the course and degree of improvement, researchers have found. Approved for use by young people 12 years of age and older, escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commonly used to treat generalized anxiety disorder (GAD) in young people, but, as with many antidepressants, the efficacy and tolerability are difficult to predict. [ABSTRACT FROM AUTHOR]

This is the first study focusing solely on that determination of tadalafil in the presence of citalopram as an antidepressant drug. The determination in biological fluids of a co‐administered antidepressant drug and a sexual stimulation drug is a very critical and important step for psychotic and ischaemic heart disease patients, especially in cases of emergency and this requires therapeutic drug monitoring. A sensitive, efficient and rapid assay was selected satisfactorily and applied for simultaneous determination of citalopram and tadalafil either in their pure forms, in tablet dosage forms or in spiked human plasma. There was a large overlap for both drugs, forming the broad band found in conventional fluorescence spectra and their related synchronous fluorescence intensity. Therefore, the development of a highly sensitive second derivative synchronous fluorescence method was demonstrated that removed this overlap. The proposed method depended on measuring the amplitudes of the second derivative of synchronous fluorescence intensity at suitable wavelengths of 301 nm and 367 nm for citalopram and tadalafil at Δλ = 60 nm, respectively. Box–Behnken design as a response surface methodology was used to fit models and create an optimization process encompassing a set of factors and resulting in an optimum response value specifically designed for this method. Under optimum conditions, the linear dynamic ranges for citalopram and tadalafil estimation were 20–900 and 5–400 ng ml−1 with detection limits of 5.40 and 1.43 ng ml−1, respectively. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 74-year-old Japanese man with frontal lobe contusion. Topics include blood tests showing no problems suggestive of dementia and neurological examination revealing no apparent motor or sensory paralysis; and experiencing no problems due to memory impairment and no psychotic symptoms such as delusions of theft being observed.

Citalopram (CIT) is a frequently used modern antidepressant that inhibits selectively serotonin reuptake in the brain. It has a chiral center in its structure and is used in therapy as both racemic mixture and pure enantiomer as its pharmacological effect is almost entirely associated with S‐CIT. The aim of this study was the development of a simple and rapid capillary electrophoresis (CE) method for the separation and quantification of CIT enantiomers. To establish the optimum chiral selector, several native and derivatized, neutral, and ionized cyclodextrins (CDs) were examined at different pH levels. An experimental design strategy was adopted for method optimization; a fractional factorial design was applied for screening purposes to identify significant experimental factors followed by a face‐centered central composite design used for optimization purposes. Computational modeling was used to obtain information on the interaction energy and the geometry of the complexes to aid in the understanding of chiral separation mechanism. The best results were obtained when using a 25‐mM phosphate buffer at pH 7.0, 3‐mM CM‐β‐CD as chiral selector, 17.5°C temperature, 15‐kV voltage, and 50 mbar/s hydrodynamic injection. The separation time was fast, below 3 min, and the migration order was S‐CIT followed by R‐CIT. The analytical performance of the method was verified in terms of precision, linearity, accuracy, sensibility, and robustness, and the method was applied for the determination of CIT enantiomers from pharmaceutical preparations. [ABSTRACT FROM AUTHOR]

Aims: Drug regulators issue safety advisories to warn clinicians and the public about new evidence of harmful effects of medicines. It is unclear how often these messages are covered by the media. Our aim was to analyse the extent of media coverage of two medicines that were subject to safety advisories from 2007 to 2016 in Australia, Canada, the United Kingdom and the United States. Methods: Two medicines widely used to treat mental health or physical conditions were selected: citalopram and denosumab. Media reports were identified by searching LexisNexis and Factiva. Reports were included if they stated at least one health benefit or harm. A content analysis of the reports was conducted. Results: In total, 195 media reports on citalopram and 239 on denosumab were included. For citalopram, 43.1% (84/195) of the reports mentioned benefits, 85.6% (167/195) mentioned harms and 9.7% (19/195) mentioned the harm described in the advisories (cardiac arrhythmia). For denosumab, 94.1% (225/239) of the reports mentioned benefits and 39.7% (95/239) mentioned harms. The harms described in the advisories were rarely mentioned: 10.9% (26/239) of the reports mentioned osteonecrosis and ≤5% mentioned any of the other harms (atypical fractures, hypocalcaemia, serious infections and dermatologic reactions). Conclusions: We found limited media coverage of the harms highlighted in safety advisories. Almost two‐thirds of the media stories on denosumab did not include any information about harms, despite the many advisories during this time frame. Citalopram coverage covered harms more often but rarely mentioned cardiac arrhythmias. These findings raise questions about how to better ensure that regulatory risk communications reach the general public. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Antidepressants increase the risk of falls and fracture in older adults. However, risk estimates vary considerably even in comparable populations, limiting the usefulness of current evidence for clinical decision making. Our aim was to apply a common protocol to cohorts of older antidepressant users in multiple jurisdictions to estimate fracture risk associated with different antidepressant classes, drugs, doses, and potential treatment indications. DESIGN: Retrospective (2009–2014) cohort study. SETTING: Five jurisdictions in the United States, Canada, United Kingdom, and Taiwan. PARTICIPANTS: Older antidepressant users—subjects were followed from first antidepressant prescription or dispensation to first fracture or until the end of follow‐up. MEASUREMENTS: The risk of fractures with antidepressants was estimated by multivariable Cox proportional hazards models using time‐varying measures of antidepressant dose and use vs nonuse, adjusting for patient characteristics. RESULTS: Between 42.9% and 55.6% of study cohorts were 75 years and older, and 29.3% to 45.4% were men. Selective serotonin reuptake inhibitors (SSRIs) (48.4%‐60.0%) were the predominant class used in North America compared with tricyclic antidepressants (TCAs) in the United Kingdom and Taiwan (49.6%‐53.6%). Fracture rates varied from 37.67 to 107.18 per 1,000. The SSRIs citalopram (hazard ratio [HR] = 1.23; 95% confidence interval [CI] = 1.11‐1.36 to HR = 1.43; 95% CI = 1.11‐1.84) and sertraline (HR = 1.36; 95% CI = 1.10‐1.68), the SNRI duloxetine (HR = 1.41; 95% CI = 1.06‐1.88), TCAs doxepin (HR = 1.36; 95% CI = 1.00‐1.86) and imipramine (HR = 1.16; 95% CI = 1.05‐1.28), and atypicals (HR = 1.34; 95% CI = 1.14‐1.58) increased fracture risk in some but not all jurisdictions. In the United States and the United Kingdom, fracture risk with all classes was higher when prescribed for depression than chronic pain, a trend that is likely explained by drug choice. CONCLUSION: The fracture risk for patients may be reduced by selecting paroxetine, an SSRI with lower risk than citalopram, the SNRI venlafaxine over duloxetine, and the TCA amitriptyline over imipramine or doxepin. There is uncertainty about the risk associated with the atypical antidepressants. J Am Geriatr Soc 68:1494‐1503, 2020. [ABSTRACT FROM AUTHOR]

A physiologically based pharmacokinetic model (PBPK) was built for citalopram using Simcyp‐based absorption, distribution, metabolism, and excretion simulator. Various physicochemical properties of citalopram were obtained from the published literature. The in vitro‐in vivo extrapolation method was used to predict clearance in humans from recombinant enzyme data. Tissue distribution was predicted using parameter estimation function to fit the developed model to the observed concentration‐versus‐time data using nonlinear mixed‐effects modeling approach. The model was verified by comparing the PBPK‐based predictions with the observed pharmacokinetic (PK) profiles of citalopram in 26 clinical studies across a dose range of 10 to 60 mg. The predicted PK parameters of citalopram after intravenous dosing were within the −10% to 22% of the corresponding PK parameters obtained from the studies with quantified data sets. Most of the predicted PK parameters of citalopram after single‐dose oral administration were within the 70%‐130% range of the corresponding PK parameters obtained from observed data from 8 studies. After multidose oral administration, percentage error of Cmax and AUC was between −21% and 25% and −31% and 21%, respectively. Most of the observed data were within the 5th and 95th percentile interval of the variability around the predicted plasma concentrations. With the established model, the PK profiles in geriatric populations, populations with cytochrome P450 (CYP) 2C19 and/or 2D6 extensive metabolizers or poor metabolizers were predicted, and the predictions were in good agreement with the observed data. The model developed is robust to represent the absorption and disposition of citalopram and can predict the impact of patient covariates, such as age and genetic polymorphism of CYP2C19 and CYP2D6, on exposure of citalopram. [ABSTRACT FROM AUTHOR]

Citalopram (CIT) is a highly selective serotonin reuptake inhibitor (SSRI) frequently used in the treatment of major depressive disorders. It has a chiral centre in its structure and is used in therapy both as a racemic mixture (R,S‐CIT) and a pure enantiomer (S‐CIT). The differences between the pharmacokinetic and pharmacological profiles of the two enantiomers are well established. Consequently, the development of new efficient chiral analysis methods for their enantiomeric separation is a topic of great actuality. CIT metabolism is stereoselective as it is metabolized in chiral active metabolites, which retain considerable SSRI activity and contribute to the pharmacological effect. Chiral analytical methods are employed for the determination of enantiomeric ratio in pharmaceutical preparations and for monitoring the enantiomer levels in biological samples for therapeutic and toxicologic purposes. The current study reviews the published literature for the chiral analysis of CIT and its metabolites based on chromatographic and electrophoretic methods coupled with UV, fluorescence and mass spectrometry detectors. [ABSTRACT FROM AUTHOR]

An analysis of 13 placebo‐controlled trials has concluded that duloxetine causes a rapid and robust reduction in depressed mood in adults with depression, with its effects not dependent on baseline severity of illness. The researchers stated that the effects of the serotonin‐norepinephrine reuptake inhibitor (SNRI) antidepressant are markedly similar to those seen with use of selective serotonin reuptake inhibitors (SSRIs). Study results were published online Sept. 14 in Neuropsychopharmacology. [ABSTRACT FROM AUTHOR]

Patients with heart disease who received the antidepressant escitalopram experienced greater improvement in anxiety symptoms compared with placebo, a 12‐week randomized trial has found. Patients in the same trial who were randomized to an aerobic exercise program experienced less consistent benefits than the escitalopram group. Study results were published online Aug. 18, 2021, in JAMA Psychiatry. [ABSTRACT FROM AUTHOR]

It will come as no surprise to practicing clinicians that shortcomings of randomized trials of newer antidepressant medications make interpretations of findings difficult. A recent meta‐analysis has found that most newer antidepressants may reduce symptoms compared to placebo, but these changes are "small and unimportant" for the majority of antidepressants, the researchers write. However, depression is a heterogeneous condition, and some patients may have a greater response. The researchers concluded that sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first‐line prescribing) could be considered as a first option. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and Huntington's disease, are considered incurable and significantly reduce the quality of life of the patients. A variety of drugs that modulate neurotransmitter levels have been used for the treatment of the neurodegenerative diseases but with limited efficacy. In this work, an amperometric complementary metal‐oxide‐semiconductor (CMOS) chip is used for high‐throughput drug testing with respect to the modulation of transmitter release from single vesicles using chromaffin cells prepared from bovine adrenal glands as a model system. Single chromaffin cell amperometry was performed with high efficiency on the surface‐modified CMOS chip and follow‐up whole‐cell patch‐clamp experiments were performed to determine the readily releasable pool sizes. We show that the antidepressant drug bupropion significantly increases the amount of neurotransmitter released in individual quantal release events. The antidepressant drug citalopram accelerates rapid neurotransmitter release following stimulation and follow‐up patch‐clamp experiments reveal that this is because of the increase in the pool of readily releasable vesicles. These results shed light on the mechanisms by which bupropion and citalopram may be potentially effective in the treatment of neurodegenerative diseases. These results demonstrate that the CMOS amperometry chip technology is an excellent tool for drug testing to determine the specific mechanisms by which they modulate neurotransmitter release. [ABSTRACT FROM AUTHOR]

Background: Drugs such as citalopram, "targeting" the serotonin pathway, can alter esophageal mechano‐chemical sensitivity and gastrointestinal motility. The aim of this study was to clarify the effect of citalopram on esophageal motility and sphincter function, transient lower esophageal sphincter relaxations (TLESRs), and reflux events. Methods: Sixteen healthy volunteers (HV) receiving 20 mg citalopram or placebo intravenously, in a randomized cross‐over fashion, underwent two high‐resolution impedance manometry studies involving liquid swallows and a high‐fat, high‐caloric meal. Manometric, reflux, and symptom‐related parameters were studied. Key Results: A lower distal contractile integral was recorded under citalopram, compared with placebo (P = 0.026). Upper esophageal sphincter (UES) resting pressure was significantly higher after citalopram administration throughout the study (P < 0.05, all periods). Similarly, the UES postswallow mean and maximum pressures were higher in the citalopram condition (P < 0.0001, in both cases) and this was also the case for the 0.2 s integrated relaxation pressure (P = 0.04). Esophagogastric junction resting pressures in the citalopram visit were significantly higher during swallow protocol, preprandial period, and the first postprandial hour (P < 0.05, in all cases). TLESRs and total reflux events were both reduced after citalopram infusion (P = 0.01, in both cases). During treatment with citalopram, five participants complained about globus sensation (P = 0.06). This citalopram‐induced globus was associated with higher UES postswallow mean and maximum pressure values (P = 0.01 and P = 0.04, respectively). Conclusions and Inferences: Administration of citalopram exerts a diversified response on esophageal motility and sphincter function, linked to clinically relevant phenomena: a reduction in postprandial TLESRs and the induction of drug‐induced globus. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na+, K+ and Ca2+, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10−9 M/L to 1.4 × 10−6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10−8 M/L, r = 0.580, P < 0.05) (F = 2.980, df1 = 6, df2 = 28, P < 0.05). Paroxetine (from 1.2 × 10−9 M/L to 5.1 × 10−5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10−8 M/L, r = 0.500, P < 0.05) (F = 2.350, df1 = 9, df2 = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments. [ABSTRACT FROM AUTHOR]

The present study involved segmental testing of hair in two clinical cases with known dosage histories. Hair analysis confirmed the first patient's exposure to the prescribed sertraline and citalopram for several months. Citalopram was generally distributed along the hair shaft in accordance with the drug ingestion period. By contrast, "false" positive results were observed for sertraline in distal hair segments, corresponding to a period of no sertraline exposure, which may indicate incorporation from sweat or sebum, which transport the drugs along the hair surface. The second patient received various drugs during her treatment for brain cancer. Metoclopramide, morphine, oxazepam, paracetamol, sumatriptan, tramadol, and zopiclone, which had been part of the therapy, were all detected in the proximal hair segment. The results of these two cases indicated that results—especially concerning the time of drug intake—must be interpreted with caution and allow for the possibility of incorporation from sweat or sebum. [ABSTRACT FROM AUTHOR]

A depression study in which 108 participants switched between classes of antidepressant after nonresponse or side effects from a first medication has added to the evidence that switching constitutes a viable strategy. Groups switching from a tricyclic antidepressant (TCA) to a selective serotonin reuptake inhibitor (SSRI), and vice versa, both saw significant improvement in depressive symptoms. Study results were published online Jan. 30 in The British Journal of Psychiatry. [ABSTRACT FROM AUTHOR]